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Hematological MalignanciesPhase 1NCT02576496

Study of Tinostamustine, First-in-Class Alkylating HDACi Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies

A Phase 1 study testing Tinostamustine in people with Hematological Malignancies and Multiple Myeloma, run by Mundipharma Research Limited at 18 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study evaluates the efficacy, safety and pharmacokinetics of tinostamustine (EDO-S101) in patients with relapsed/refractory hematologic malignancies. All patients will receive tinostamustine. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tinostamustine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
106 participants
Where
18 sitesin 7 countries
Study dates
14 Apr 2016to 21 Nov 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient willing and able to sign an informed consent.
  • Patients age ≥18 years at signing the informed consent.
  • Life expectancy > 3 months.
  • Diagnosis of relapsed or refractory lymphoid malignancy for which there are no available therapies.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Absolute Neutrophil Count >1,000 µL
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  • Platelets ≥100,000 µL
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 upper limit of normal (ULN).
  • Total bilirubin <2.0 mg/dL unless elevated due to known Gilbert's syndrome.
  • Creatinine ≤1.5 x ULN.
  • Serum potassium and magnesium at least at the lowest limit of normal (LLN) at baseline(before every IMP administration; if it is below LNN, (supplementation is permissible).
  • Males and females of child-bearing potential, and their partners, must be willing to use at least two effective forms of birth control during the study drug administration and for at least 90 days after the administration of the study drug to be eligible to participate. Vasectomized partners and patients must be willing to use a secondary method of effective birth control. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
  • Specific Eligibility Criteria for Each Patient Cohort in Stage 2 Phase of the Study
  • Cohort 1: relapsed/refractory multiple myeloma (Recruitment to this cohort stopped Dec 2021) 1. At least one line of prior systemic therapy and no other standard therapy available with proven clinical benefit.
  • Cohort 2: relapsed/refractory Hodgkin's lymphoma
  • 1. At least two lines of prior therapy and no other standard therapy available with proven clinical benefit.
  • Cohort 3: PTCL (recruitment to this cohort stopped March 2021)
  • Only PTCL patients with histologically or cytologically confirmed Peripheral T-Cell Lymphoma - Not Otherwise Specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), or Anaplastic Large Cell Lymphoma (ALCL).
  • At least one line of prior combination therapy and no other standard therapy available with proven clinical benefit
  • Cohort 4: relapsed/refractory cutaneous T-cell lymphoma (CTCL), subtypes mycosis fungoides (MF) and Sézary syndrome (SS)
  • Only CTCL patients with histologically or cytologically confirmed MF or SS with stage IIb to IVb disease based on modified ISCL/EORTC staging.
  • At least one line and a maximum of four prior standard systemic therapies and no other standard therapy available with proven clinical benefit.
  • Cohort 5: PTCL (Recruitment to this cohort stopped March 2021)
  • Eligibility criteria for sub study:
  • Diagnosis of relapsed or refractory lymphoma, including Diffuse large B cell lymphoma who failed at least 2 lines of prior systemic therapy, Hodgkin lymphoma who failed at least 3 lines of prior systemic therapy, follicular lymphoma grade 1-3a, marginal zone lymphoma and mantle cell lymphoma who failed at least 2 lines of prior systemic lines of prior therapy, T cell lymphoma (including PTCL, CTCL) who failed at least 2 lines of prior systemic therapy for which there are no available therapies. Patients with bulky disease and Multiple Myeloma patients are excluded from this sub study.

Who cannot join

  • Patients with any central nervous system involvement.
  • Patient who had a hematologic malignancy that has transformed.
  • Any patient who has relapsed within 100 days of stem cell infusion following an allogenic or an autologous bone marrow transplant.
  • Patients with corrected QT (QTc) interval (Fridericia's formula) > 450 msec.
  • Patients who are on treatment with drugs known to prolong the QT/QTc interval.
  • Any serious medical condition that interferes with adherence to study procedures.
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  • Patients with a history of another malignancy diagnosed within three years of study enrollment excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  • Pregnant or breast feeding females.
  • New York Heart Association (NYHA) stage III/IV congestive heart failure. The following arrhythmias not adequately controlled, active: atrial fibrillation/flutter with poor rate control, documented sustained ventricular tachycardia (defined as >30 seconds or requiring cardioversion before 30 seconds have elapsed) or TdP.
  • Active infections, or other significant co-morbidities [(e.g., active central nervous system metastases and/or carcinomatous meningitis, active infection requiring systemic therapy, history of human immunodeficiency virus (HIV) infection, or active Hepatitis B or Hepatitis C.
  • Previous cancer therapies within three (3) weeks of dosing as long as the patient has recovered to eligibility levels prior to treatment in this study.
  • Use of other investigational agents within 30 days or 5 half-lives prior to the first dose of study drug unless patient has recovered from any related toxicities ≥ Grade 1.
  • Steroid treatment within seven (7) days prior to study treatment. Patients that require intermittent use of bronchodilators, topical steroids or local steroid injections will not be excluded from the study. Patients who have been stabilized to 10 mg PO QD or less seven (7) days prior to study drug administration are allowed.
  • Patients on Valproic Acid for any indication (epilepsy, mood disorder) must be excluded from the trial .

Trial locations and contacts

18 sites in 7 countries.

18 sites in 7 countries

France5 sites

  • CHU de Caen

    Caen, CS 3001

  • CHU ESTAING Service de thérapie Cellulaire et hématologique Clinique

    Clermont-Ferrand, 63000

  • CHU Lille Service des Maladies du Sang

    Lille, 59037

  • Hopital Haut Leveque

    Pessac, 33604

  • Centre hospitalier Lyon Sud

    Pierre-Bénite, 69495

Other trials in France

United States4 sites

  • University Hospitals Cleveland Seidman Cancer Center

    Cleveland, Ohio, 44106

  • Mayo Clinic Cancer Center

    Jacksonville, Florida, 32224

  • Columbia University Medical Center

    New York, New York, 10019

  • Mayo Clinic

    Phoenix, Arizona, 85054

Other trials in United States

Spain3 sites

  • Institut Català d'Oncologia de Barcelona

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario Marqués de Valdecilla

    Santander, 39008

Other trials in Spain

Italy2 sites

  • Institute of Hematology "L. A. Seràgnoli", University of Bologna

    Bologna, 40138

  • National Cancer Institute, Fondazione 'G. Pascale'

    Naples, I-80131

Other trials in Italy

Netherlands2 sites

  • VU medisch centrum

    Amsterdam, 1081 HV

  • Erasmus MC

    Rotterdam, 3015 GD

Other trials in Netherlands

Germany1 site

  • University Hospital of Ulm, Department of Internal Medicine III

    Ulm, 89081

Other trials in Germany

Switzerland1 site

  • Kantonsspital St.Gallen

    Sankt Gallen, 9007

Other trials in Switzerland

About this study

Official title: A Phase 1 Trial to Investigate the Safety, Pharmacokinetic Profiles and the Efficacy of Tinostamustine, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies

This study evaluates the efficacy, safety and pharmacokinetics of tinostamustine (EDO-S101) in patients with relapsed/refractory hematologic malignancies. All patients will receive tinostamustine.

Read the detailed description

Tinostamustine is a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule. It is anticipated that tinostamustine may have activity in various hematological malignancies and solid tumors.

This study is a multi-centre, open-label phase 1 study of single agent EDO-S101 in subjects with relapsed/refractory haematological malignancies and for whom no other therapies are available.

The study consists of 2 stages and 1 sub-study:

  • Stage 1: Dose Escalation to determine Maximum Tolerated Dose (MTD) at the optimal infusion time and the pharmacokinetic (PK) profiles; is expected to enroll between 21 and 48 patients. Stage 1 has now been completed.
  • Stage 2: Expansion in five Cohorts, in which approximately 12-16 patients will be enrolled per cohort, for a maximum of 70 patients.

In Stage 1, tinostamustine doses were escalated following the standard 3+3 design. The decision to escalate to the next dose level occurred after all cohort patients completed 3 weeks (21 days) of observation and have been evaluated for safety and toxicity. The starting dose was a 1 hour infusion of 20 mg/m2, and the maximum dose level was 150 mg/m2. Reduced infusion times of 45 minutes and 30 minutes were assessed once the maximum tolerated dose at a 1-hour infusion was determined.

In Stage 2, five cohorts of patients (with relapsed/refractory multiple myeloma (MM); relapsed/refractory Hodgkin's lymphoma; relapsed/refractory peripheral T-cell lymphoma (PTCL); relapsed/refractory cutaneous T-cell lymphoma (CTCL); and relapsed/refractory T-cell Prolymphocytic leukemia (T-PLL) will be enrolled and treated at the recommended Phase 2 dose (RP2D) based on results of Stage 1. For MM patients, treatment will occur on Day 1 and Day 15 of a 28 day cycle. For lymphoma patients, treatment will occur on Day 1 of a 21 day cycle. Patients in each stage of the study are expected to receive a median of four Cycles of therapy, and the maximum number of treatment Cycles allowed is 12.

A sub study portion was added to the protocol as an amendment. In the sub study 6-12 patients will be treated with 100mg/m2 tinostamustine infusion delivered over 100 minutes.

Being tested
Tinostamustine
Keywords
phase 1 clinical trial, multiple myeloma, Hodgkin's lymphoma, cutaneous T-cell lymphoma, tinostamustine
Medical subject headings
Hematologic Neoplasms, Multiple Myeloma, Hodgkin Disease, Lymphoma, T-Cell, Cutaneous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TinostamustineDrug

    Also called EDO-S101

Study groups in NCT02576496
Study groupRoleWhat they receive
Tinostamustine 20mg/m2 over 60minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 40mg/m2 over 60minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 60mg/m2 over 60minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 80mg/m2 over 60minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 100mg/m2 over 60minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 120mg/m2 over 60minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 80mg/m2 over 45minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 60mg/m2 over 30minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Tinostamustine 80mg/m2 over 30minExperimentalTinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Stage 2 cohort 1: relapsed/refractory Multiple MyelomaExperimentalTinostamustine as a single agent administered at a dose of 60mg/m2 by IV infusion over 60min on D1 and D15 of 28-day cycle.
Receives: Drug: Tinostamustine
Stage 2 cohort 2: relapsed/refractory Hodgkin LymphomaExperimentalTinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Stage 2 cohort 3: relapsed/refractory peripheral T-cell lymphoma (PTCL)ExperimentalTinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
Stage 2 cohort 4: relapsed/refractorycutaneous T-cell lymphoma (CTCL)ExperimentalTinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle. Patients are of subtypes mycosis fungoides (MF) or Sézary syndrome (SS).
Receives: Drug: Tinostamustine
Stage 2 cohort 5: relapsed/refractory T-cell Prolymphocytic leukemia (T-PLL)ExperimentalTinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle.
Receives: Drug: Tinostamustine
SubstudyExperimentalTinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 100min on D1 of 21-day cycle.
Receives: Drug: Tinostamustine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate

    Determine overall response rate

    Measured: 10-20 months from beginning of stage 2

  2. Clinical benefit rate by cohort

    Determine clinical benefit rate by cohort

    Measured: 10-20 months from beginning of stage 2

Secondary outcomes (4)

  1. Time to objective response

    Evaluate time to objective response by cohort

    Measured: 10-20 months after beginning stage 2

  2. Duration of response

    Evaluate duration of response

    Measured: 10-20 months after beginning stage 2

  3. Progression free survival (PFS)

    Determine time to progression free survival time for patients who received the RP2D

    Measured: 32-36 months after beginning stage 2

  4. Overall Survival (OS)

    Determine the overall survival time for patients who received the RP2D

    Measured: 32-36 months after beginning stage 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2015 (estimated)
  2. Study start14 Apr 2016
  3. Primary completion30 May 2023
  4. Study completion21 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02576496
Sponsor's protocol ID
EDO-S101-1001
Status last verified
Jul 2024
First submitted
12 Oct 2015
Last updated
25 Jul 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Relevant patient listing data of de-identified patients may be reviewed

Publications

  • Sureda A, Pinto A, Ghesquieres H, Morschhauser F, Tournilhac O, Mutsaers P, Zijlstra JM, De Filippi R, Hilgier K, Manamley N, Janik T, Zinzani PL. Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial. Hematol Oncol. 2025 Jan;43(1):e70000. doi: 10.1002/hon.70000.

    PubMed 39617826

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tinostamustine in people with Hematological Malignancies and Multiple Myeloma, run by Mundipharma Research Limited at 18 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in France, United States, Spain, Italy, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (time frame: 10-20 months from beginning of stage 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02576496, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.

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